Transcriptomic Signatures of Single-Suture Craniosynostosis Phenotypes.
Transcriptomic Signatures of Single-Suture Craniosynostosis Phenotypes.
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DOI：
10.3390/ijms24065353
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发表时间：
2023-03-10
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
颅缝早闭是一种出生缺陷，颅骨缝过早闭合，作为遗传综合征的一部分或独立，原因不明。本研究旨在确定与对照组相比，来自四种单缝颅缝早闭表型患者的原代颅骨细胞系中基因表达的差异。颅骨重建手术期间从临床部位采集颅骨样本（N = 388例/85例对照）。然后从组织中获得原代细胞系并用于RNA测序。与对照组相比，线性模型拟合估计协变量调整后的基因表达与四种单缝颅缝早闭表型（颅缝早闭、额裂、矢状和冠状）之间的相关性。还对每种表型进行了性别分层分析。差异表达基因（DEG）包括72个与冠状相关的基因，90个与矢状相关的基因，103个与间位相关的基因，和33个与颅缝早闭相关的基因。性别分层分析显示，男性（98）的DEG多于女性（4）。有16个DEG为同源异型盒（HOX）基因。三种TF（SUZ 12、EZH 2、AR）显著调节DEG在一种或多种表型中的表达。通路分析确定了四个KEGG通路与至少一种颅缝早闭的表型。总之，这项工作提出了与颅缝早闭症表型和胎儿性别相关的独特分子机制。
Craniosynostosis is a birth defect where calvarial sutures close prematurely, as part of a genetic syndrome or independently, with unknown cause. This study aimed to identify differences in gene expression in primary calvarial cell lines derived from patients with four phenotypes of single-suture craniosynostosis, compared to controls. Calvarial bone samples (N = 388 cases/85 controls) were collected from clinical sites during reconstructive skull surgery. Primary cell lines were then derived from the tissue and used for RNA sequencing. Linear models were fit to estimate covariate adjusted associations between gene expression and four phenotypes of single-suture craniosynostosis (lambdoid, metopic, sagittal, and coronal), compared to controls. Sex-stratified analysis was also performed for each phenotype. Differentially expressed genes (DEGs) included 72 genes associated with coronal, 90 genes associated with sagittal, 103 genes associated with metopic, and 33 genes associated with lambdoid craniosynostosis. The sex-stratified analysis revealed more DEGs in males (98) than females (4). There were 16 DEGs that were homeobox (HOX) genes. Three TFs (SUZ12, EZH2, AR) significantly regulated expression of DEGs in one or more phenotypes. Pathway analysis identified four KEGG pathways associated with at least one phenotype of craniosynostosis. Together, this work suggests unique molecular mechanisms related to craniosynostosis phenotype and fetal sex.
影响因子：
2.9
作者：
Gonzalez PN;Kristensen E;Morck DW;Boyd S;Hallgrímsson B
通讯作者：
Hallgrímsson B